This Article Order Full text via Infotrieve Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Zhang, J. Articles by Ferrans, V. J. Search for Related Content PubMed PubMed Citation Articles by Zhang, J. Articles by Ferrans, V. J.

American Journal of Pathology, Vol 142, 1916-1926, Copyright © 1993 by American Society for Investigative Pathology

REGULAR ARTICLES

Dendritic cells in the hearts of spontaneously hypertensive rats treated with doxorubicin with or without ICRF-187

J Zhang, EH Herman and VJ Ferrans
Division of Research and Testing, Food and Drug Administration, Laurel, Maryland.

Histological and immunohistochemical studies using specific monoclonal antibodies were made to evaluate the severity of the chronic cardiomyopathy and the quantitative changes in interstitial dendritic cells (antigen-presenting cells), T helper lymphocytes, T cytotoxic/suppressor lymphocytes, and macrophages in the hearts of spontaneously hypertensive rats (SHRs) treated with doxorubicin at 1 mg/kg per week for 3, 6, 9 or 12 weeks. In addition, an assessment was made of the modifications of the responses of these cell populations by pretreatment of the SHR with ICRF-187, which protects against doxorubicin cardiotoxicity. The number of interstitial dendritic cells/mm2 of section of left ventricle was similar in saline-treated control SHRs (76 +/- 6) and in those treated with ICRF-187 alone (75 +/- 2) but increased markedly (319 +/- 33) in animals receiving a total cumulative dose of 12 mg/kg doxorubicin. Treatment with ICRF-187 prior to each administration of doxorubicin attenuated in a dose-dependent manner the increase in numbers of dendritic cells induced by doxorubicin (231 +/- 47, 174 +/- 11, and 100 +/- 16 cells/mm2) after treatment with 6.25, 12.5, and 25 mg of ICRF-187, respectively. Doxorubicin also induced increases in the numbers of T helper lymphocytes and macrophages but not of T cytotoxic/suppressor lymphocytes. These increases were also attenuated by pretreatment with ICRF-187. These data were interpreted as indicating that doxorubicin cardiotoxicity results in the release of substances that initiate immune reactions involving the antigen-presenting cells of the heart and that such reactions are attenuated by pretreatment with ICRF-187.

This article has been cited by other articles:

				Jun Zhang, E. H. Herman, D. G. Robertson, M. D. Reily, A. Knapton, H. V. Ratajczak, N. Rifai, R. Honchel, K. T. Blanchard, R. E. Stoll, et al. Mechanisms and Biomarkers of Cardiovascular Injury Induced by Phosphodiesterase Inhibitor III SK&F 95654 in the Spontaneously Hypertensive Rat Toxicol Pathol, February 1, 2006; 34(2): 152 - 163. [Abstract] [PDF]

				E. F. Petricoin, V. Rajapaske, E. H. Herman, A. M. Arekani, S. Ross, D. Johann, A. Knapton, J. Zhang, B. A. Hitt, T. P. Conrads, et al. Toxicoproteomics: Serum Proteomic Pattern Diagnostics for Early Detection of Drug Induced Cardiac Toxicities and Cardioprotection Toxicol Pathol, January 1, 2004; 32(1_suppl): 122 - 130. [Abstract] [PDF]

				J. Yamate, K. Sato, M. Ide, M. Nakanishi, M. Kuwamura, S. Sakuma, and S. Nakatsuji Participation of Different Macrophage Populations and Myofibroblastic Cells in Chronically Developed Renal Interstitial Fibrosis after Cisplatin-induced Renal Injury in Rats Vet. Pathol., May 1, 2002; 39(3): 322 - 333. [Abstract] [Full Text] [PDF]

				O. J. Arola, A. Saraste, K. Pulkki, M. Kallajoki, M. Parvinen, and L.-M. Voipio-Pulkki Acute Doxorubicin Cardiotoxicity Involves Cardiomyocyte Apoptosis Cancer Res., April 1, 2000; 60(7): 1789 - 1792. [Abstract] [Full Text]

				S. E. Lipshultz, N. Rifai, S. E. Sallan, S. R. Lipsitz, V. Dalton, D. B. Sacks, and M. E. Ottlinger Predictive Value of Cardiac Troponin T in Pediatric Patients at Risk for Myocardial Injury Circulation, October 21, 1997; 96(8): 2641 - 2648. [Abstract] [Full Text]